Is DEFB129 p.Pro165= (c.495T>A) pathogenic?

DEFB129 p.Pro165= (c.495T>A) is classified Likely benign in DEFB129 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD v4.1; Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with DEFB129 p.Pro165= (c.495T>A)?

DEFB129 p.Pro165= (c.495T>A) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is DEFB129 p.Pro165= (c.495T>A) in the general population?

DEFB129 p.Pro165= (c.495T>A) is absent from gnomAD v4.1 (gnomAD).

DEFB129 p.Pro165=

c.495T>A · rs2514218860 · VCV2681233

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

EBV-positive nodal T- and NK-cell lymphoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.029	GERP -2.5
Overall
CADD	1.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DEFB129
Protein: p.Pro165=
Coding: c.495T>A
MANE Select: NM_080831
dbSNP: rs2514218860
Type: single nucleotide variant
Location: chr20:229714 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 60.57
Residue 165: the 'disordered' region

Full DEFB129 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

DEFB129 p.Ala163Pro Likely benign same condition
DEFB129 p.Ala163Val Uncertain significance ★ ⚠ same type
DEFB129 p.Arg26Cys Uncertain significance ★ ⚠ same type
DEFB129 p.Arg26His Uncertain significance ★ ⚠ same type
DEFB129 p.Asn73Lys Uncertain significance ★ ⚠ same type
DEFB129 p.Asp154His Uncertain significance ★ ⚠ same type
DEFB129 p.Glu178Asp Uncertain significance ★ ⚠ same type
DEFB129 p.Glu182Lys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/defb129-p-pro165 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown